Evaluación del uso de fármacos y conducta en pacientes con síndrome X frágil / Asessment of pharmacological freatment and behavioral changes in patients with fragile X syndrome

El Síndrome X Frágil (SXF) es la principal causa heredada de Discapacidad intelectual (DI) y Trastorno del espectro autista (TEA). Se caracteriza por presentar un fenotipo conductual asociado a hiperactividad, déficit atencional, impulsividad, ansiedad, trastornos conductuales, espectro autista y retraso global del desarrollo. No existe actualmente un tratamiento farmacológico para el trastorno genético de base. El tratamiento farmacológico se focaliza en los síntomas que interfieren con la calidad de vida y aprendizaje, entre ellos la irritabilidad e hiperactividad. OBJETIVO: Evaluar cambios conductuales a través de la escala conductual ABC, de pacientes masculinos con diagnóstico de SXF tratados con psicoestimulantes y/o antipsicóticos en comparación a controles. MÉTODO: Se evalúa a 40 pacientes hombres con diagnóstico de SXF entre los años 2014 y 2017. Se utiliza la evaluación de la conducta mediante el puntaje en la subescala de irritabilidad e hiperactividad de la encuesta ABC-C y el registro de fármacos indicados. Se compara la sintomatología conductual en pacientes que no utilizan fármacos, aquellos que utilizan antipsicóticos, los que usan psicoestimulantes y pacientes tratados con ambos fármacos. RESULTADOS: La mediana de edad fue de 15,1 (±9,3) años. Del total de pacientes, el 42,5% reportó uso de fármacos, de éstos el 35% utilizó psicoestimulantes, 35% antipsicóticos y 30% la combinación de ambos. Se observa que solo el grupo que recibe tratamiento con psicoestimulantes y antipsicóticos en forma simultánea presenta diferencias con el subgrupo sin tratamiento farmacológico. CONCLUSIONES: En más de la mitad de nuestros pacientes se decide no utilizar tratamiento farmacológico. Sin embargo, dichos pacientes igualmente presentan sintomatología de irritabilidad e hiperactividad. Los pacientes que recibieron terapia asociada de psicoestimulantes y antipsicóticos presentan puntajes significativamente más altos en la escala de irritabilidad que aquellos que no recibieron tratamiento farmacológico. Este grupo, que constituye el 12,5% del total de la muestra, presenta un fenotipo conductual que genera mayores dificultades en la calidad de vida del paciente y su entorno.

Fragile X Syndrome (FXS) is the main inherited cause of Intellectual Disability and Autism Spectrum Disorder. It characteristically presents as a behavioral phenotype asso- ciated with hyperactivity, attention deficit, impulsivity, anxiety, behavioral disorders, autistic spectrum and global developmental delay. There is currently no pharmacological treatment for the underlying genetic disorder. Pharmacological treatment targets symptoms that interfere with quality of life and learning, including irritability and hyperactivity.OBJECTIVE: To evaluate behavioral changes through the ABC behavioral scale of male patients diagnosed with FXS treated with psychostimulants and / or antipsychotics compared to controls. METHOD: 40 male patients with a diagnosis of FXS between 2014 and 2017 were evaluated. The behavioral assessment was done by scoring the irritability and hyperactivity subscale of the ABC-C survey and by registering the prescribed drug. Behavioral symptomatology was compared in patients who do not use drugs, those who use antipsychotics, those who use psychostimulants and patients treated with both drugs. RESULTS: The median age was 15.1 (± 9.3) years. Of the total of patients, 42.5% were prescribed drugs, of these 35% used psychostimulants, 35% antipsychotics and 30% the combination of both. It was observed that the group that received treatment with both psychostimulants and antipsychotics simultaneously presented differences with the subgroup without pharmacological treatment.CONCLUSIONS: In more than half of our patients no pharmacological treatment is prescribed. However, these patients also show symptoms of irritability and hyperactivity. Patients who received associated therapy of psychostimulants and antipsychotics have significantly higher scores on the irritability scale than those who did not receive pharmacological treatment. This group, which constitutes 12.5% of the total sample, has a behavioral phenotype that generates greater difficulties in the patient's quality of life and their environment.

Caries experience and salivary aspects in individuals with fragile X syndrome

Abstract Fragile X syndrome (FXS) is the most common cause of hereditary mental retardation, but studies on the oral health condition of these patients are rare. The aim of this study was to determine the experience of dental caries in individuals with FXS, by examining the saliva profile, oral hygiene, socioeconomic characteristics and use of controlled drugs in these patients. Dental health was estimated using the decayed, missing and filled teeth index (DMF-T) and sialometry, and the pH value and buffering capacity of the saliva, colony forming units of S. mutans (CFU/mL), visible biofilm index, and socioeconomic status were all examined. The sample, comprising 23 individuals, had an average age of 17.3 ± 5.6 years, a DMF-T index of 5.5, a diminished salivary flow (78.3%), and a low (73.9%) saliva buffering capacity. Most (52.2%) individuals presented with a high abundance (CFU/mL) of S. mutans. The experience of caries was correlated with salivary parameters, poor oral hygiene, lower socioeconomic status and an increased count of S. mutans in saliva.

Avaliação de estratégia combinada de eletroforese capilar e PCR triplo metilação-específica para diagnóstico molecular da Síndrome do X Frágil / Assessment of a combined strategy of capillary electrophoresis and methylation-specific triple polymerase chain reaction for molecular diagnosis of the Fragile X Syndrome

Introdução: a síndrome do X frágil é a principal causa de retardo mental de natureza familiar. Suas características clínicas pouco marcantes fazem com que um diagnóstico de certeza a partir de testes moleculares seja imprescindível. Objetivo: descrever e avaliar as vantagens e desvantagens de uma estratégia combinada de PCR triplo metilação-específica e eletroforese capilar para o diagnóstico molecular da síndrome do X frágil, visando baixo custo, exequibilidade, reprodutibilidade e sensibilidade. Métodos: foram coletadas 43 amostras de sanguede pacientes com déficit cognitivo e de suas mães, quando indicado. Tais indivíduos possuíam exame citogenético positivo, fenótipo e/ou história familiar sugestivas de síndrome do X frágil. Após extração de DNA, foi realizada eletroforese capilar com marcadores fluorescentes,tratamento com bissulfito de sódio e três reações de PCR metilação-específicas em cada amostra. Resultados: foi possível determinar o genótipo em 29 pacientes: 23 (14 homens e nove mulheres) apresentavam alelos com tamanho normal e seis (todos do sexo masculino) possuíam alelos na faixa de mutação completa. Em outras seis amostras, todas do sexo feminino, foi possível determinar um alelo na faixa normal e outro alelo alterado, entretanto, sem diferenciação entre faixa de pré-mutação ou de mutação completa. Nas demais oito amostras(cinco homens e três mulheres), não se pôde determinar o genótipo. Conclusões: a técnica proposta faz uma triagem de pacientes, mas apresenta desvantagens, como não terem sido obtidos resultados satisfatórios com as reações para alelos metilados e a análise dos rastrosdas PCRs com três primers ter se mostrado difícil e dependente de observador.

Introduction: The fragile X syndrome is the main cause of inherited mental retardation. Its very small remarkable clinical characteristics make that a surely diagnosis from molecular tests be indispensable. Objective: To describe and assess the advantages and disadvantages of a combined strategy of methylation-specific triple polymerase chain reaction (PCR)and capillary electrophoresis for the molecular diagnosis of the fragile X syndrome, seeking low cost, feasibility, reproducibility, and sensibility. Methods: 43 blood samples were collected from patients with cognitive deficit and their mothers, when indicated. Such subjects presented a positive cytogenetic exam, phenotype and/or familiar history suggestive of the fragile X syndrome. After DNA extraction, capillary electrophoresis with fluorescent markers, treatment with sodium bisulfite, and three methylation-specific PCR reactions were performed in each sample. Results: It was possible to determine the genotype in 29 patients: 23 (14 men and 9 women) presented alleles with normal size and six (all male) had them in the complete mutation range. In other six female samples, it was possible to determine an allele in the normal range and another altered; nevertheless, without differentiation between the pre-mutation or complete mutation ranges. In the other eight samples (five men and threewomen), it was not possible to establish the genotype. Conclusions: The suggested technique does a patient?s screening, but it has some disadvantages such as non-satisfying results been seen with the reactions for methylated alleles and analysis of the PCRs tracks with three primers being difficult and dependent on the observer.

The fragile x-associated tremor and ataxia syndrome (FXTAS) / A síndrome de tremor e ataxia associada ao X frágil (FXTAS)

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.

A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.